Efficacy of subsequent treatments in patients who progressed to mCRPC following treatment with apalutamide for nonmetastatic castration-resistant prostate cancer (nmCRPC): A post-hoc analysis of the SPARTAN phase III trial.

Abstract

157 Background: Apalutamide (Apa) delays the onset of metastases and extends survival in nmCRPC. However, the benefit of subsequent therapy for metastatic castration resistant prostate cancer (mCRPC) following progression on Apa remains inadequately explored. Methods: A post-hoc analysis of SPARTAN, a randomized phase III (NCT01946204), double-blind, placebo-controlled trial with Apa for the treatment of men with nmCRPC was undertaken in order to assess the impact of post-protocol treatment. Patients included in this analysis were SPARTAN patients who developed mCRPC while on Apa and received a first subsequent therapy for mCRPC (the “Next Cohort”). The index date of the analysis was the initiation of first subsequent treatment for mCRPC. The baseline characteristics of the Next Cohort (reported from the time of initial randomization because updated characteristics at the index date could not be derived) were compared to those of the ITT Apa arm in SPARTAN. Subsequent overall survival (sOS) and subsequent progression-free survival per physician assessment (sPFS) were calculated from the index date using Kaplan-Meier method. Results: At study completion, 237 patients remained on Apa without progression, while 311 were included in the Next Cohort. Of these, 241 (77.5%) received abiraterone acetate plus prednisone (AAP) provided by the sponsor as an option as first subsequent treatment, 29 (9.3%) received docetaxel; 20 (6.4%) enzalutamide and 21 other treatments (6.8%). Compared to the ITT Apa arm in SPARTAN, a higher proportion of the Next Cohort had PSA doubling time ≤6 months (79.1% vs 71.5%) and a PSA value above median at baseline, and experienced poorer PSA response (51% PSA90 overall response rate vs 62%) whilst on apalutamide treatment. The median sPFS and sOS were 6.8 months (95% confidence interval, CI, 5.8-7.9) and 20.0 months (95% CI, 17.0-22.6), respectively. Choice of subsequent next treatment did not appear to have an impact on sPFS and sOS. Conclusions: Limitations of this analysis include its retrospective nature and the lack of randomization to first line mCRPC therapy and related potential confounding, and the inclusion of patients who had progressed at SPARTAN study completion with associated poorer prognosis. Nevertheless, the analysis suggests comparable efficacy of selected first line mCRPC therapies, following progression on Apa for nmCRPC. Clinical trial information: NCT01946204 . [Table: see text]